Olive oil phenols inhibit human hepatic microsomal activity.

We have examined the inhibition of human hepatic microsomal androstenedione 6beta-hydroxylation and both reductive and oxidative 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity by complex phenols found in olive oil. Structurally similar compounds were also examined for comparison. Androstenedione 6beta-hydroxylase activity was inhibited by oleuropein glycoside, hydroxytyrosol and gallic acid. Oleuropein glycoside, hydroxytyrosol, gallic acid and dihydroxybenzoic acid also inhibited reductive 17beta-HSD activity. Oxidative 17beta-HSD activity was not inhibited by any of the compounds tested; however gallic acid stimulated activity by approximately 30%. Androstenedione 6beta-hydroxylase activity showed atypical kinetics. For oleuropein glycoside, hydroxytyrosol and gallic acid the apparent K(i) values were determined to be 80, 77 and 70 micromol/L, respectively. Analysis of structural features of inhibitory compounds established that a 3,4-dihydroxyphenyl ethanol structure was required for inhibition of androstenedione 6beta-hydroxylase for this group of compounds.